Malaria is a major human health concern in many tropical and sub-tropical regions, and current antimalarial drugs are becoming increasingly ineffective due to emerging and spreading resistance. Plasmodium falciparum, the most deadly human malaria parasite, poses a major threat to human health worldwide, with over 500 million clinical cases and 1-3 million deaths annually. Snow et al., “The global distribution of clinical episodes of Plasmodium falciparum malaria,” Nature 434:241-217 (2005).
Natural products and their synthetic derivatives have provided the greatest number of successful antimalarial treatments to date, representing approximately 65% of prescribed drugs. Newman et al., “Natural products as sources of new drugs over the last 25 years,” J Nat Prod 70:461-477 (2007). Quinine, discovered from cinchona tree bark, has been used to treat malaria since the 17th century and was the primary antimalarial drug until it was replaced by chloroquine, a synthetic derivative, in the 1940s. Hyde, “Drug-resistant malaria,” Trends Parasitol 21:494-498 (2005). Chloroquine became the mainstay antimalarial agent until resistant strains began to appear over a decade after its introduction. Artemisinin, isolated from the plant Artemisia annua used in traditional Chinese medicine, ushered in a new wave of antimalarials and became the most potent and rapid-acting drug available. Klayman, “Qinghaosu (artemisinin)—an antimalarial drug from China,” Science 228:1049-1055 (1985). Several artemisinin synthetic derivatives have since been developed, and artemisinin-based combination therapies are currently being used throughout the world to treat this parasitic disease. However, artemisinin-resistant strains have recently been reported (Dondorp et al., “Artemisinin resistance in Plasmodium falciparum malaria,” N Engl J Med 361:455-467 (2009)), and new antiparasitic drugs are urgently needed to combat these strains.